Abstract: The effect of three-day course of hyperbaric oxygenation (HBO; 3 atm, 50 min, 1 session per day) on glutamine metabolism in the liver has been investigated in 72 adult albino rats. The content of ammonia, glutamate, glutamine, activity of glutamine synthetase (GS), phosphate-dependent glutaminase (PDG), and glutamate dehydrogenase (GDH) were studied in left (LLL) and median (MLL) lobes of the liver. The course of HBO had an inhibitory effect on all the enzymes studied. Inhibitory effect of hyperoxia on GDH activity persisted up to day 11 after the course of HBO in both lobes of the liver, while decreased glutamate normalized in both lobes. Reduced glutamine concentration normalized to day 4, and the concentration of ammonia and remained elevated for 11 days after the end of hyperoxic exposure. Inhibitory effect of hyperoxia on GS activity in LLL and MLL disappeared on day 4 and day 11 day after the end of the HBO course. PDG activity reduced by HBO in both lobes normalized to the day 4 day after oxygenation; however, on day 11 it selectively decreased in LLL, where simultaneous stimulation of GS activity was also observed. The results demonstrate different sensitivity of liver GS, PDG and GDH of normal rats to the inhibitory effect of HBO. Different dynamics of GS and PDG activity in LLL and MLL of oxygenated rats suggests functional heterogeneity of the glutamine cycle in hepatocytes of liver lobes after HBO